Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury

Álvarez, Zaida; Kolberg-Edelbrock, Alexandra N; Sasselli, Ivan R.; Ortega, Joaquı́n M.; Qiu, Ruomeng; Syrgiannis, Zois; Mirau, Peter A.; Chen, F.; Chin, Stacey M.; Weigand, Steven; Kiskinis, Evangelos; Stupp, Samuel I.

doi:10.1126/science.abh3602

Cited by 169 publications

(172 citation statements)

References 50 publications

Supporting

Mentioning

169

Contrasting

Order By: Relevance

“…However, determining and modeling the effective charge density is crucial for understanding the PA self-assembly behavior and to optimize the sample processing conditions for a particular application. Furthermore, recent studies have shown that the molecular dynamics is critical for the PA nanostructures to form hierarchical structures ( Freeman et al, 2018 ; Stupp et al, 2020 ; Wester et al, 2020 ) and to optimize biological signaling ( Álvarez et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Acid-Base Equilibrium and Dielectric Environment Regulate Charge in Supramolecular Nanofibers

et al. 2022

View full text Add to dashboard Cite

Peptide amphiphiles are a class of molecules that can self-assemble into a variety of supramolecular structures, including high-aspect-ratio nanofibers. It is challenging to model and predict the charges in these supramolecular nanofibers because the ionization state of the peptides are not fixed but liable to change due to the acid-base equilibrium that is coupled to the structural organization of the peptide amphiphile molecules. Here, we have developed a theoretical model to describe and predict the amount of charge found on self-assembled peptide amphiphiles as a function of pH and ion concentration. In particular, we computed the amount of charge of peptide amphiphiles nanofibers with the sequence C16 − V2A2E2. In our theoretical formulation, we consider charge regulation of the carboxylic acid groups, which involves the acid-base chemical equilibrium of the glutamic acid residues and the possibility of ion condensation. The charge regulation is coupled with the local dielectric environment by allowing for a varying dielectric constant that also includes a position-dependent electrostatic solvation energy for the charged species. We find that the charges on the glutamic acid residues of the peptide amphiphile nanofiber are much lower than the same functional group in aqueous solution. There is a strong coupling between the charging via the acid-base equilibrium and the local dielectric environment. Our model predicts a much lower degree of deprotonation for a position-dependent relative dielectric constant compared to a constant dielectric background. Furthermore, the shape and size of the electrostatic potential as well as the counterion distribution are quantitatively and qualitatively different. These results indicate that an accurate model of peptide amphiphile self-assembly must take into account charge regulation of acidic groups through acid–base equilibria and ion condensation, as well as coupling to the local dielectric environment.

show abstract

Section: Introductionmentioning

confidence: 99%

Acid-Base Equilibrium and Dielectric Environment Regulate Charge in Supramolecular Nanofibers

et al. 2022

View full text Add to dashboard Cite

show abstract

“…SCI is a severely debilitating condition that results in significant loss of sensory and motor function [40][41][42]. Extensive research has focused on identification of medications that can promote functional and pathological recovery following spinal cord injury [43][44][45].…”

Section: Discussionmentioning

confidence: 99%

Aucubin promoted neuron functional recovery by suppressing inflammation and neuronal apoptosis in a spinal cord injury model

Xiao

Zhong

Yang

et al. 2022

Preprint

View full text Add to dashboard Cite

Spinal cord injury (SCI) can cause severe motor impairment. Post-SCI treatment has focused primarily on secondary injury, with neuroinflammation and neuronal apoptosis as the primary therapeutic targets. Aucubin (Au), a Chinese herbal medicine, exerts anti-inflammatory and neuroprotective effects. The therapeutic effects of Au in SCI have not been reported. We showed that Au can promote functional recovery after SCI. Recovery may occur through the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway to promote M2/M1 polarization in microglia and inhibit mitochondrial dysfunction to reduce neuronal apoptosis. These biochemical changes result in reduced secondary injury and facilitate axon regeneration. Therefore, Au may be a promising post-SCI therapeutic medication.

show abstract

“… 15 In this regard, using bioactive supramolecular polymers, the Stupp group has recently shown that the dynamics of monomer association within supramolecular polymers plays a key role in the repair of spinal cord injury. 51 …”

Section: Supramolecular Polymers Made Of Aromatic-peptide Conjugatesmentioning

confidence: 99%

Hierarchical self-assembly of aromatic peptide conjugates into supramolecular polymers: it takes two to tango

2022

View full text Add to dashboard Cite

show abstract

Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury

Cited by 169 publications

References 50 publications

Acid-Base Equilibrium and Dielectric Environment Regulate Charge in Supramolecular Nanofibers

Acid-Base Equilibrium and Dielectric Environment Regulate Charge in Supramolecular Nanofibers

Aucubin promoted neuron functional recovery by suppressing inflammation and neuronal apoptosis in a spinal cord injury model

Hierarchical self-assembly of aromatic peptide conjugates into supramolecular polymers: it takes two to tango

Contact Info

Product

Resources

About